(1) Field of the Invention
The present invention relates to a novel pharmaceutical composition. More specifically, the present invention relates to a stable solid pharmaceutical composition comprising a benzimidazole compound.
(2) Description of Related Art
Some benzimidazole compounds have a proton pump inhibitory action, and are widely employed as a therapeutic drug for gastric ulcers, reflux esophagitis, duodenal ulcers, anastomotic ulcers, Zollinger-Ellison syndrome and the like. It is thought that proton pump inhibitors exhibit the above-described pharmacological action by inhibiting the activity of the proton pump located at the final stage of the gastric acid secretion mechanism in the parietal cells of the gastric mucosa.
However, some benzimidazole compounds are unstable against acid or water and are susceptible to decomposing. Accordingly, a pharmaceutical composition which contains such a benzimidazole compound may decompose during storage from the action of an acidic substance in the drug product formulation or may decompose from gastric acid when taken internally in the stomach, whereby the desired pharmacological activity cannot be obtained.
Therefore, when producing a pharmaceutical composition which contains the above-described benzimidazole compound, it is necessary to take special measures, such as ensuring the compound does not come into contact with an acidic substance, blending with an alkaline substance or making into an enteric formulation in which the drug does not dissolve in the stomach.
Various investigations have been carried out for the purpose of stabilizing such unstable benzimidazole compounds.
Related art documents which illustrate the investigative results include the following.
For example, JP-A-62-277322 describes a pharmaceutical composition composed of a basic inorganic salt of magnesium and/or calcium blended in a benzimidazole or derivative thereof having antiulcer activity. Further, JP-A-62-258316 describes an oral pharmaceutical drug product formulation comprising an acid-unstable compound such as omeprazole, wherein the drug product formulation contains a core containing an acid-unstable compound and an alkali-reactive compound, an intermediate layer containing a tablet excipient which is soluble in water or rapidly decomposable in water or a water-soluble film-forming compound which is a polymer, and an enteric coating.
JP-A-2003-192579 describes granules comprising a principal ingredient layer containing an acid-unstable medicament such as proton pump inhibitor in an amount of about 12% by weight or more based on the total amount, an intermediate coating layer formed on the principal ingredient layer, and an enteric coating formed on the intermediate coating layer, wherein the granules contain a basic inorganic salt and have an average particle size of about 600 μm or more.
JP-A-2001-199873 describes a sustained-release pellet comprising: (a) an inert core; (b) an active layer disposed over the inert core, formed from a benzimidazole compound, an inert, non-basic polymer soluble in water and one or more pharmaceutically acceptable inert excipients; (c1) an intermediate layer which is formed from an inert, non-basic polymer soluble in water and one or more pharmaceutically acceptable inert excipients; (c2) an intermediate layer having a system of modified release which comprises an inert, non-basic polymer soluble in water and a non-basic polymer insoluble in water; and (d) an exterior layer comprising an enteric coating.
WO 2005/011637 describes a pharmaceutical composition characterized by having, on a core substance, a layer (1) containing crospovidone, a layer (2) containing sodium hydroxide which is adjacent to the layer containing crospovidone, and a layer (3) containing a benzimidazole compound or a pharmacologically acceptable salt thereof which is adjacent to the layer containing sodium hydroxide.